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Advanced Sequencing Allows Fuller Picture of Primate Genomes

New advances in sequencing technology and assembly has allowed researchers to get the clearest and most detailed picture yet of the Western Iowland gorilla’s genome. The findings could have implications in understanding evolution and human diseases.

The team, led by Evan Eichler, professor of genome sciences at the University of Washington used Single Molecule, Real-Time (SMRT) sequencing technology, along with tools Falcon and Quiver to assemble the genome, creating long sequence reads that are over a hundred times the length of the most used sequence technologies. The researchers analyzed DNA from the blood of female Western Iowland gorilla, Susie, from the Lincoln Park Zoo in Chicago.

While advances have made short-read sequencing technology less expensive and increased throughput, the presence of repetitive DNA, common in humans and primates, makes whole-genome assembly problematic.

Although the Western Lowland gorilla’s genome has been sequenced before, there were many gaps and short-read technology meant it was broken into more than 400,000 fragments.

“Such assemblies can be like Swiss cheese, with a lot of missing biological information in the gaps,” Eichler said in a university announcement. Using the new approach there are now only 1,800 pieces.

Ninety percent of all gaps in the original genome assembly were closed this time around, and each genome fragment was, on average, 800 times larger.

The new information allowed them to find previously undetected genes and thousands of protein- and peptide-coding segments.

In terms of evolutionary similarity to humans, the Iowland gorilla is second only to chimps. Eichler said he believes there if far more genetic variation than previously thought that distinguishes humans from the great apes, and that all of the great ape genomes should be re-sequenced and assembled to get a comprehensive view.

Genetic variation may explain why human ancestors followed a different evolutionary path than their great ape ancestors.

The scientists found interesting differences between gorillas and humans in genes associated with sensory perception, the production of keratin, insulin regulation, immunity, reproduction and cell signaling.

The more complete genome assembly also provided new insight into the evolutionary history of the Iowland gorilla by shedding light on the severity of a bottleneck in the gorilla population not that long ago.

Eichler said that this method of sequencing can bolster research on the genetic underpinnings of human disease if more human genomes are sequenced that way, noting that depending on only short read sequences does not give the full picture.

“Long read sequencing is allowing us to access new levels of genetic variation that were previously inaccessible,” he said.